Administration of recombinant human erythropoietin (rhEpo) stimulates erythropoiesis and increases red[unreadable] Dlood cell half-life, resulting in an increased hematocrit and potentially reducing the need for allogeneic blood[unreadable] transfusions in the critically ill patient. The original impetus for this project was to be able to control for these[unreadable] ystemic effects of rhEpo administration when examining the effects of rhEpo on cerebrovascular[unreadable] dysfunction in PROJECT 1. However, these effects on the occurrence and severity of anemia and on the[unreadable] need for blood transfusions may actually have equal or greater importance for long-term outcome than the[unreadable] neuroprotective effects.[unreadable] Patients with severe traumatic brain injury (TBI), like all critically ill patients, commonly develop anemia[unreadable] during the acute recovery period. Anemia after severe trauma is the result of a complex interaction of[unreadable] Dleeding, blunted Epo response to low hemoglobin concentrations, inflammatory mediators, and a[unreadable] hypoferremic state. Anemia requires the injured brain to maintain a higher cerebral blood flow (CBF) to[unreadable] maintain the same level of oxygen delivery. Cerebrovascular dysfunction caused by the trauma may prevent[unreadable] an adequate increase in CBF, which is the normal compensatory mechanism for a reduced oxygen-carrying[unreadable] capacity. Even if CBF does increase to maintain cerebral oxygen delivery, the resulting cerebral[unreadable] vasodilatation required to achieve the increase in CBF may result in an increased intracranial pressure (ICP).[unreadable] To optimize cerebral oxygenation in critically ill brain-injured patients, it is commonly recommended that[unreadable] hemoglobin concentration be maintained at approximately 10 g/dl. However, there is very little evidence that[unreadable] this practice actually improves cerebral hemodynamics or oxygenation, and maintaining hematocrit at this[unreadable] level commonly requires transfusion of blood products which may have significant risk.[unreadable] Trauma is the most common cause of death in the 1-44 yr age group, and the third most common cause[unreadable] for the entire US population. Trauma accounts for more loss of work life-years than cancer and[unreadable] cardiovascular diseases combined. Effective treatments for this important public health disorder are needed.[unreadable] We propose to study the role that erythropoietin administration might play in maintaining cerebral[unreadable] oxygenation after TBI. The specific aims include the following: 1-To study the role of anemia of critical[unreadable] illness on brain oxygenation and cerebral hemodynamics (including ICP) after TBI. 2-To study the[unreadable] complications associated with transfusion of blood products in patients with TBI. 3-To study the role of[unreadable] rhEpo administration on reducing the need for blood transfusion after TBI.